STAT3 and neoplasm: In this respect, since, through IL-1β signaling, TG2 is an activator of NF-kB [29, 30] and a critical mediator of IL-6 production in luminal-type breast cancer, and since TG2 is highly expressed in drug-resistant cancer cells [31], TG2 may function as a component of the positive feedback loop between NF-kB and IL-6/STAT3, which mediates cancer aggressiveness and hormone-independent tumor growth.